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1.
Br J Clin Pharmacol ; 90(1): 107-126, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37559444

RESUMO

AIMS: Several medicinal treatments for avoiding postoperative ileus (POI) after abdominal surgery have been evaluated in randomized controlled trials (RCTs). This network meta-analysis aimed to explore the relative effectiveness of these different treatments on ileus outcome measures. METHODS: A systematic literature review was performed to identify RCTs comparing treatments for POI following abdominal surgery. A Bayesian network meta-analysis was performed. Direct and indirect comparisons of all regimens were simultaneously compared using random-effects network meta-analysis. RESULTS: A total of 38 RCTs were included in this network meta-analysis reporting on 6371 patients. Our network meta-analysis shows that prokinetics significantly reduce the duration of first gas (mean difference [MD] = 16 h; credible interval -30, -3.1; surface under the cumulative ranking curve [SUCRA] 0.418), duration of first bowel movements (MD = 25 h; credible interval -39, -11; SUCRA 0.25) and duration of postoperative hospitalization (MD -1.9 h; credible interval -3.8, -0.040; SUCRA 0.34). Opioid antagonists are the only treatment that significantly improve the duration of food recovery (MD -19 h; credible interval -26, -14; SUCRA 0.163). CONCLUSION: Based on our meta-analysis, the 2 most consistent pharmacological treatments able to effectively reduce POI after abdominal surgery are prokinetics and opioid antagonists. The absence of clear superiority of 1 treatment over another highlights the limits of the pharmacological principles available.


Assuntos
Íleus , Antagonistas de Entorpecentes , Humanos , Metanálise em Rede , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Íleus/tratamento farmacológico , Íleus/etiologia , Íleus/prevenção & controle
2.
Colorectal Dis ; 23(6): 1451-1462, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33624371

RESUMO

AIM: Postoperative morbidity is high in patients operated on for Crohn's disease (CD) complicated by malnutrition. This study aimed to evaluate the impact of preoperative enteral nutritional support (PENS) on postoperative outcome in patients with CD complicated by malnutrition included in a prospective nationwide cohort. METHOD: Malnutrition was defined as body mass index <18 kg/m2 and/or albuminaemia <30 g/L and/or weight loss >10%. Failure of PENS was defined as the requirement for additional preoperative parenteral nutrition to PENS. Univariate analysis of the risk factors for PENS failure was performed. Propensity score matching (PSM) was used to compare the outcomes between 'upfront surgery' and 'PENS' groups. The primary endpoint was the rate of intra-abdominal septic morbidity and/or temporary defunctioning stoma. RESULTS: Among 592 patients included, 149 were selected. In the intention-to-treat population including 20 (13.4%) patients with PENS failure after PSM, 78 'upfront surgery' and 71 'PENS'-matched patients were compared, with no significant difference in the primary endpoint. Perforating CD and preoperative intra-abdominal fistula were associated with PENS failure [37.5 vs 16.1% (P = 0.047) and 41.2% vs 16.2% (P = 0.020), respectively]. After exclusion of these 20 patients, PSM was used to compare 45 'upfront surgery' and 51 'PENS'-matched patients, with a significantly decreased rate of intra-abdominal septic complications and/or temporary defunctioning stoma in the PENS group (19.6 vs 42.2%, P = 0.016). CONCLUSION: Preoperative enteral nutritional support is associated with a trend but no conclusive evidence of a reduction in intra-abdominal septic complications and/or requirement for defunctioning stoma. Patients with perforating CD complicated with malnutrition are at risk of PENS failure.


Assuntos
Doença de Crohn , Desnutrição , Doença de Crohn/complicações , Doença de Crohn/cirurgia , Humanos , Desnutrição/etiologia , Desnutrição/terapia , Apoio Nutricional , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Sistema de Registros
3.
Ann Surg ; 270(5): 827-834, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31567506

RESUMO

OBJECTIVE: The aim of this study was to assess recurrence risk factors following ileocolonic resection (ICR) for Crohn disease (CD) in a nationwide cohort study SUMMARY BACKGROUND DATA:: Recurrence rate after ICR for CD can be up to 60%, but its predictive factors have never been evaluated in large prospective cohort studies. METHODS: From 2013 to 2015, 346 consecutive patients undergoing ICR for CD and a postoperative ileocoloscopy within 6 to 12 months after surgery at 19 academic French centers were included prospectively. RESULTS: Twelve-month postoperative endoscopic (Rutgeerts score ≥i2) and clinical recurrence rates were 57.6% [95% confidence interval (CI), 54.2-61.0] and 11.3% (95% CI, 9-13.6), respectively. A total of 185 patients (54%) had a postoperative CD prophylaxis, comprising thiopurine in 69 (20%), or anti-tumor necrosis factor (TNF) therapy in 93 (27%). In multivariate Cox regression analysis, absence of postoperative smoking {odds ratio [OR] = 0.60 (95% CI, 0.40-0.91); P = 0.016}, postoperative prophylaxis [OR = 0.60 (95% CI, 0.41-0.88); P = 0.009], and penetrating disease behavior [OR = 0.58 (95% CI, 0.39-0.86); P = 0.007] were the only independent predictors of reduced endoscopic recurrence risk. Postoperative prophylaxis [OR 0.31 (95% CI, 0.15-0.66); P = 0.002), and penetrating behavior [OR = 00.36 (95% CI, 0.16-0.81); P = 0.013), were the only independent predictors of reduced clinical recurrence risk. Postoperative anti-TNF therapy was associated with a significant reduction of both 12-month risks of endoscopic (P < 0.001) and clinical (P = 0.019) recurrences. CONCLUSION: Absence of postoperative smoking, CD prophylaxis, and penetrating disease behavior could be independent predictors of reduced postoperative recurrence after ICR for CD. Prophylactic anti-TNF therapy reduces both endoscopic and clinical recurrence rates. It suggests that upfront surgery followed by postoperative anti-TNF therapy is probably the best therapeutic approach for complex CD (penetrating disease behavior).


Assuntos
Colo/cirurgia , Doença de Crohn/diagnóstico , Doença de Crohn/cirurgia , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Íleo/cirurgia , Perfuração Intestinal/cirurgia , Centros Médicos Acadêmicos , Adulto , Análise de Variância , Anastomose Cirúrgica/métodos , Estudos de Coortes , Bases de Dados Factuais , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Feminino , França , Humanos , Incidência , Perfuração Intestinal/diagnóstico , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/fisiopatologia , Prognóstico , Estudos Prospectivos , Recidiva , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto Jovem
4.
Ann Surg ; 267(2): 221-228, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29300710

RESUMO

OBJECTIVE: To determine the risk factors of morbidity after surgery for ileocolonic Crohn disease (CD). SUMMARY BACKGROUND DATA: The risk factors of morbidity after surgery for CD, particularly the role of anti-TNF therapy, remain controversial and have not been evaluated in a large prospective cohort study. METHODS: From 2013 to 2015, data on 592 consecutive patients who underwent surgery for CD in 19 French specialty centers were collected prospectively. Possible relationships between anti-TNF and postoperative overall morbidity were tested by univariate and multivariate analyses. Because treatment by anti-TNF is possibly dependent on the characteristics of the patients and disease, a propensity score was calculated and introduced in the analyses using adjustment of the inverse probability of treatment-weighted method. RESULTS: Postoperative mortality, overall and intra-abdominal septic morbidity rates in the entire cohort were 0%, 29.7%, and 8.4%, respectively; 143 (24.1%) patients had received anti-TNF <3 months prior to surgery. In the multivariate analysis, anti-TNF <3 months prior to surgery was identified as an independent risk factor of the overall postoperative morbidity (odds-ratio [OR] =1.99; confidence interval [CI] 95% = 1.17-3.39, P = 0.011), with preoperative hemoglobin <10 g/dL (OR = 4.77; CI 95% = 1.32-17.35, P = 0.017), operative time >180 min (OR = 2.71; CI 95% = 1.54-4.78, P < 0.001) and recurrent CD (OR = 1.99; CI 95% = 1.13-3.36, P = 0.017). After calculating the propensity score and adjustment according to the inverse probability of treatment-weighted method, anti-TNF <3 months prior to surgery remained associated with a higher risk of overall (OR = 2.98; CI 95% = 2.04-4.35, P <0.0001) and intra-abdominal septic postoperative morbidities (OR = 2.22; CI 95% = 1.22-4.04, P = 0.009). CONCLUSIONS: Preoperative anti-TNF therapy is associated with a higher risk of morbidity after surgery for ileocolonic CD. This information should be considered in the surgical management of these patients, particularly with regard to the preoperative preparation and indication of temporary defunctioning stoma.


Assuntos
Anticorpos Monoclonais/efeitos adversos , Doença de Crohn/cirurgia , Fármacos Gastrointestinais/efeitos adversos , Complicações Pós-Operatórias/induzido quimicamente , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/uso terapêutico , Terapia Combinada , Doença de Crohn/tratamento farmacológico , Feminino , Fármacos Gastrointestinais/uso terapêutico , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Período Pré-Operatório , Estudos Prospectivos , Fatores de Risco , Resultado do Tratamento , Adulto Jovem
5.
Clin Gastroenterol Hepatol ; 13(10): 1770-5, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26001338

RESUMO

BACKGROUND & AIMS: Colonic strictures complicate inflammatory bowel disease (IBD) and often lead to surgical resection to prevent dysplasia or cancer. We assessed the frequency of dysplasia and cancer among IBD patients undergoing resection of a colorectal stricture. METHODS: We analyzed data from the Groupe d'études et thérapeutiques des affections inflammatoires du tube digestif study. This was a nationwide retrospective study of 12,013 patients with IBD in France who underwent surgery for strictures at 16 centers from August 1992 through January 2014 (293 patients for a colonic stricture, 248 patients with Crohn's disease, 51% male, median age at stricture diagnosis of 38 years). Participants had no preoperative evidence of dysplasia or cancer. We collected clinical, endoscopic, surgical, and pathology data and information on outcomes. RESULTS: When patients were diagnosed with strictures, they had IBD for a median time of 8 years (3-14). The strictures were a median length of 6 cm (4-10) and caused symptoms in 70% of patients. Of patients with Crohn's disease, 3 (1%) were found to have low-grade dysplasia, 1 (0.4%) was found to have high-grade dysplasia, and 2 (0.8%) were found to have cancer. Of patients with ulcerative colitis, 1 (2%) had low-grade dysplasia, 1 (2%) had high-grade dysplasia, and 2 (5%) had cancer. All patients with dysplasia or cancer received curative surgery, except 1 who died of colorectal cancer during the follow-up period. No active disease at time of surgery was the only factor associated with dysplasia or cancer at the stricture site (odds ratio, 4.86; 95% confidence interval, 1.11-21.27; P = .036). CONCLUSIONS: In a retrospective study of patients with IBD undergoing surgery for colonic strictures, 3.5% were found to have dysplasia or cancer. These findings can be used to guide management of patients with IBD and colonic strictures.


Assuntos
Neoplasias do Colo/epidemiologia , Constrição Patológica/complicações , Doenças Inflamatórias Intestinais/complicações , Lesões Pré-Cancerosas/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , França/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Adulto Jovem
6.
Transpl Int ; 28(12): 1371-82, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26303035

RESUMO

The incidence and consequences of de novo donor-specific anti-HLA antibodies (DSAs) after liver transplantation (LT) are not well known. We investigated the incidence, risk factors, and complications associated with de novo DSAs in this setting. A total of 152 de novo liver-transplant patients, without preformed anti-HLA DSAs, were tested for anti-HLA antibodies, with single-antigen bead technology, before, at transplantation, at 1, 3, 6 and 12 months after transplantation, and thereafter annually and at each time they presented with increased liver-enzyme levels until the last follow-up, that is, 34 (1.5-77) months. Twenty-one patients (14%) developed de novo DSAs. Of these, five patients had C1q-binding DSAs (24%). Younger age, low exposure to calcineurin inhibitors, and noncompliance were predictive factors for de novo DSA formation. Nine of the 21 patients (43%) with de novo DSAs experienced an acute antibody-mediated rejection (AMR). Positive C4d staining was more frequently observed in liver biopsies of patients with AMR (9/9 vs. 1/12, P < 0.0001). Eight patients received a B-cell targeting therapy, and one patient received polyclonal antibodies. Only one patient required retransplantation. Patient- and graft-survival rates did not differ between patients with and without DSAs. In conclusion, liver-transplant patients with liver abnormalities should be screened for DSAs and AMR.


Assuntos
Rejeição de Enxerto/imunologia , Antígenos HLA/imunologia , Isoanticorpos/sangue , Transplante de Fígado/efeitos adversos , Adolescente , Adulto , Idoso , Especificidade de Anticorpos , Feminino , Seguimentos , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fatores de Tempo , Doadores de Tecidos , Adulto Jovem
7.
Cancers (Basel) ; 14(3)2022 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-35158797

RESUMO

Proctocolectomy with ileal pouch-anal anastomosis is the intervention of choice for ulcerative colitis and familial adenomatous polyposis requiring surgery. One of the long-term complications is pouch cancer, having a poor prognosis. The risk of high-grade dysplasia and cancer in the anal transitional zone and ileal pouch after 20 years is estimated to be 2 to 4.5% and 3 to 10% in ulcerative colitis and familial polyposis, respectively. The risk factors for ulcerative colitis are the presence of pre-operative dysplasia or cancer, disease duration > 10 years and severe villous atrophy. For familial polyposis, the risk factors are the number of pre-operative polyps > 1000, surgery with stapled anastomosis and the duration of follow-up. In the case of ulcerative colitis, a pouchoscopy should be performed annually if one of the following is present: dysplasia and cancer at surgery, primary sclerosing cholangitis, villous atrophy and active pouchitis (every 5 years without any of these factors). In the case of familial polyposis, endoscopy is recommended every year including chromoendoscopy. Even if anal transitional zone and ileal pouch cancers seldom occur following proctectomy for ulcerative colitis and familial adenomatous polyposis, the high mortality rate associated with this complication warrants endoscopic monitoring.

8.
Cancers (Basel) ; 13(4)2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33578769

RESUMO

BACKGROUND: Abdominoperineal resection (APR) and pelvic exenteration (PE) for the treatment of cancer require extensive pelvic resection with a high rate of postoperative complications. The objective of this work was to systematically review and meta-analyze the effects of vertical rectus abdominis myocutaneous flap (VRAMf) and mesh closure on perineal morbidity following APR and PE (mainly for anal and rectal cancers). METHODS: We searched PubMed, Cochrane, and EMBASE for eligible studies as of the year 2000. After data extraction, a meta-analysis was performed to compare perineal wound morbidity. The studies were distributed as follows: Group A comparing primary closure (PC) and VRAMf, Group B comparing PC and mesh closure, and Group C comparing PC and VRAMf in PE. RESULTS: Our systematic review yielded 18 eligible studies involving 2180 patients (1206 primary closures, 647 flap closures, 327 mesh closures). The meta-analysis of Groups A and B showed PC to be associated with an increase in the rate of total (Group A: OR 0.55, 95% CI 0.43-0.71; p < 0.01/Group B: OR 0.54, CI 0.17-1.68; p = 0.18) and major perineal wound complications (Group A: OR 0.49, 95% CI 0.35-0.68; p < 0.001/Group B: OR 0.38, 95% CI 0.12-1.17; p < 0.01). PC was associated with a decrease in total (OR 2.46, 95% CI 1.39-4.35; p < 0.01) and major (OR 1.67, 95% CI 0.90-3.08; p = 0.1) perineal complications in Group C. CONCLUSION: Our results confirm the contribution of the VRAMf in reducing major complications in APR. Similarly, biological prostheses offer an interesting alternative in pelvic reconstruction. For PE, an adapted reconstruction must be proposed with specialized expertise.

9.
Front Cell Dev Biol ; 8: 363, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32582690

RESUMO

Inflammatory Bowel Diseases (IBD) are chronic inflammatory disorders, where epithelial defects drive, at least in part, some of the pathology. We reconstituted human intestinal epithelial organ, by using three-dimension culture of human colon organoids. Our aim was to characterize morphological and functional phenotypes of control (non-IBD) organoids, compared to inflamed organoids from IBD patients. The results generated describe the epithelial defects associated with IBD in primary organoid cultures, and evaluate the use of this model for pharmacological testing of anti-inflammatory approaches. Human colonic tissues were obtained from either surgical resections or biopsies, all harvested in non-inflammatory zones. Crypts were isolated from controls (non-IBD) and IBD patients and were cultured up to 12-days. Morphological (size, budding formation, polarization, luminal content), cell composition (proliferation, differentiation, immaturity markers expression), and functional (chemokine and tight junction protein expression) parameters were measured by immunohistochemistry, RT-qPCR or western-blot. The effects of inflammatory cocktail or anti-inflammatory treatments were studied in controls and IBD organoid cultures respectively. Organoid cultures from controls or IBD patients had the same cell composition after 10 to 12-days of culture, but IBD organoid cultures showed an inflammatory phenotype with decreased size and budding capacity, increased cell death, luminal debris, and inverted polarization. Tight junction proteins were also significantly decreased in IBD organoid cultures. Inflammatory cytokine cocktail reproduced this inflammatory phenotype in non-IBD organoids. Clinically used treatments (5-ASA, glucocorticoids, anti-TNF) reduced some, but not all parameters. Inflammatory phenotype is associated with IBD epithelium, and can be studied in organoid cultures. This model constitutes a reliable human pre-clinical model to investigate new strategies targeting epithelial repair.

10.
J Crohns Colitis ; 13(12): 1510-1517, 2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31051502

RESUMO

BACKGROUND AND AIMS: To compare perioperative characteristics and outcomes between primary ileocolonic resection [PICR] and iterative ileocolic resection [IICR] for Crohn's disease [CD]. METHODS: From 2013 to 2015, 567 patients undergoing ileocolonic resection were prospectively included in 19 centres of the GETAID chirurgie group. Perioperative characteristics and postoperative results of both groups [431 PICR, 136 IICR] were compared. Uni- and multivariate analyses of the risk factors of overall 30-day postoperative morbidity was carried out in the IICR group. RESULTS: IICR patients were less likely to be malnourished [27.2% vs 39.9%, p = 0.007], and had more stricturing forms [69.1% vs 54.3%, p = 0.002] and less perforating disease [19.9% vs 39.2%, p < 0.001]. Laparoscopy was less commonly used in IICR [45.6% vs 84.5%, p < 0.01] and was associated with increased conversion rates [27.4% vs 14.6%, p = 0.012]. Overall postoperative morbidity was 36.8% in the IICR group and 26.7% in the PICR group [p = 0.024]. There was no significant difference between IICR and PICR regarding septic intra-abdominal complications, anastomotic leakage [8.8% vs 8.4%] or temporary stoma requirement. IICR patients were more likely to present with non-infectious complications and ileus [11.8% vs 3.7%, p < 0.001]. Uni- and multivariate analyses did not identify specific risk factors of overall postoperative morbidity in the IICR group. CONCLUSIONS: Surgery for recurrent CD is associated with a slight increase of non-infectious morbidity [postoperative ileus] that mainly reflects the technical difficulties of these procedures. However, IICR remains a safe therapeutic option in patients with recurrent CD because severe morbidity including anastomotic complications is similar to patients undergoing primary resection. PODCAST: This article has an associated podcast which can be accessed at https://academic.oup.com/ecco-jcc/pages/podcast.


Assuntos
Colectomia , Doença de Crohn/cirurgia , Íleo/cirurgia , Complicações Pós-Operatórias , Reoperação , Idoso , Anastomose Cirúrgica/efeitos adversos , Anastomose Cirúrgica/métodos , Colectomia/efeitos adversos , Colectomia/métodos , Colectomia/estatística & dados numéricos , Doença de Crohn/diagnóstico , Feminino , França/epidemiologia , Humanos , Íleo/patologia , Masculino , Avaliação de Processos e Resultados em Cuidados de Saúde , Complicações Pós-Operatórias/classificação , Complicações Pós-Operatórias/cirurgia , Recidiva , Reoperação/métodos , Reoperação/estatística & dados numéricos , Índice de Gravidade de Doença
11.
Am J Surg ; 189(6): 720-9, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15910726

RESUMO

BACKGROUND: Only 2 large (more than 100 patients) prospective trials comparing pancreatogastrostomy (PG) with pancreatojejunostomy (PJ) after pancreatoduodenectomy (PD) have been reported until now. One nonrandomized study showed that there were less pancreatic and digestive tract fistula with PG, whereas the other, a randomized trial from a single high-volume center, found no significant differences between the two techniques. METHODS: Single blind, controlled randomized, multicenter trial. The main endpoint was intra-abdominal complications (IACs). RESULTS: Of 149 randomized patients, 81 underwent PG and 68 PJ. No significant difference was found between the two groups concerning pre- or intraoperative patient characteristics. The rate of patients with one or more IACs was 34% in each group. Twenty-seven patients sustained a pancreatoenteric fistula (18%), 13 in PG (16%; 95% confidence interval [CI] 8-24%) and 14 in PJ (20%; 95% CI 10.5-29.5%). No statistically significant difference was found between the 2 groups concerning the mortality rate (11% overall), the rate of reoperations and/or postoperative interventional radiology drainages (23%), or the length of hospital stay (median 20.5 days). Univariate analysis found the following risk factors: (1) age > or =70 years old, (2) extrapancreatic disease, (3) normal consistency of pancreas, (4) diameter of main pancreatic duct <3 mm, (5) duration of operation >6 hours, and (6) a center effect. Significantly more IAC, pancreatoenteric fistula, and deaths occurred in one center (that included the most patients) (P = .05), but there were significantly more high-risk patients in this center (normal pancreas consistency, extrapancreatic pathology, small pancreatic duct, higher transfusion requirements, and duration of operation >6 hours) compared with the other centers. In multivariate analysis, the center effect disappeared. Independent risk factors included duration of operation >6 hours for IAC and for pancreatoenteric fistula (P = .01), extrapancreatic disease for pancreatoenteric fistulas (P < .04), and age > or =70 years for mortality (P < .02). CONCLUSIONS: The type of pancreatoenteric anastomosis (PJ or PG) after PD does not significantly influence the rate of patients with one or more IAC and/or pancreatic fistula or the severity of complications.


Assuntos
Gastrostomia , Pancreatectomia , Pancreaticoduodenectomia , Pancreaticojejunostomia , Complicações Pós-Operatórias/epidemiologia , Adulto , Fatores Etários , Idoso , Drenagem , Feminino , França/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Reoperação , Fatores de Risco , Método Simples-Cego , Fatores de Tempo
12.
Ann Transplant ; 19: 76-81, 2014 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-24509827

RESUMO

BACKGROUND: Patients with a simultaneous pancreas-kidney transplant (SPKT), especially those with gastroparesis, often have gastro-intestinal (GI) disorders that can modify immunosuppressant pharmacokinetics. We compared the MPA 12-hours area under the curve (AUC(0-12)) in SKPT patients with severe gastroparesis receiving mycophenolate mofetil (MMF) or enteric-coated mycophenolate sodium (EC-MPS). MATERIAL/METHODS: Fifteen SKPT patients having a severe gastroparesis were switched, at 182 (69-1523) days post-transplantation, from MMF to EC-MPS because of GI disorders. MPA AUC(0-12) values were obtained before and after the switch, ie, under MMF (500 mg b.i.d.) at 169 (51-1522) days post-transplantation and EC-MPS (360 mg b.i.d.) at 102 (26-355) days after the switch. RESULTS: Mean MPA AUC(0-12) h did not differ significantly under MMF and EC-MPS, ie, 40.13±14 and 38.24±15.5 mg*h/L, respectively. Trough and maximal MPA concentrations were similar with both MPA formulations. Although all patients had GI disorders under MMF (100%), only 3 had persistent GI disorders under EC-MPS (20%) (p<0.001). CONCLUSIONS: In SKPT patients with severe gastroparesis, exposure to MPA is similar under MMF and EC-MPS. However, the incidence of GI disorders is significantly lower when patients are given EC-MPS.


Assuntos
Imunossupressores/farmacocinética , Transplante de Rim , Ácido Micofenólico/análogos & derivados , Transplante de Pâncreas , Comprimidos com Revestimento Entérico/farmacocinética , Adulto , Diabetes Mellitus Tipo 1/cirurgia , Diabetes Mellitus Tipo 2/cirurgia , Nefropatias Diabéticas/cirurgia , Feminino , Seguimentos , Gastroparesia/tratamento farmacológico , Rejeição de Enxerto/tratamento farmacológico , Humanos , Imunossupressores/administração & dosagem , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Ácido Micofenólico/farmacocinética , Estudos Retrospectivos , Comprimidos com Revestimento Entérico/administração & dosagem , Adulto Jovem
13.
Dig Liver Dis ; 44(6): 515-22, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22480969

RESUMO

BACKGROUND: Recommended strategies to screen for Lynch syndrome in colorectal cancer are not applied in daily practice and most of Lynch cases remain undiagnosed. AIMS: We investigated in routine conditions a strategy that uses simplified clinical criteria plus detection of MisMatch Repair deficiency in tumours to identify Lynch carriers. METHODS: Colorectal cancer patients that met at least one of three clinical criteria were included: (1) colorectal cancer before 50 years, (2) personal history of colorectal or endometrial cancer, (3) first-degree relative history of colorectal or endometrial cancer. All tumours underwent an MisMatch Repair test combining microsatellite instability analysis and MisMatch Repair immunohistochemistry. Patients with an MisMatch Repair-deficient tumour were offered germline testing. RESULTS: Of the 307 patients fulfilling the clinical criteria, 46 (15%) had a MisMatch Repair-deficient tumour. Amongst them 27 were identified as Lynch carriers (20 with germline mutation: 12 MLH1, 7 MSH2, 1 MSH6; 7 highly suspected cases despite failure of genetic testing). The simplified clinical criteria selected a population whose MisMatch Repair-deficient status was highly predictive (59%) of Lynch syndrome. CONCLUSION: This bio-clinical strategy based on simplified clinical criteria combined with an MisMatch Repair test efficiently detected LS cases and is easy to use in clinical practice, outside expert centres.


Assuntos
Adenocarcinoma/diagnóstico , Adenocarcinoma/genética , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Neoplasias Colorretais Hereditárias sem Polipose/genética , Neoplasias do Endométrio/genética , Testes Genéticos , Proteínas Adaptadoras de Transdução de Sinal/genética , Adulto , Fatores Etários , Reparo de Erro de Pareamento de DNA , Análise Mutacional de DNA , Proteínas de Ligação a DNA/genética , Feminino , Mutação em Linhagem Germinativa , Humanos , Imuno-Histoquímica , Masculino , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Proteína 1 Homóloga a MutL , Proteína 2 Homóloga a MutS/genética , Proteínas Nucleares/genética , Seleção de Pacientes , Valor Preditivo dos Testes , Proteínas Proto-Oncogênicas B-raf/genética
14.
Inflamm Bowel Dis ; 17(3): 747-57, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20684014

RESUMO

BACKGROUND: In human pathology, the "creeping fat" (CF) of the mesentery is unique to Crohn's disease (CD). CF is usually referred to as an ectopic extension of mesenteric adipose tissue (MAT). However, since no animal model developing CF has ever been established, very little is known about this type of fat-depot expansion and its role in the development of the disease. METHODS: We developed and standardized an experimental protocol in mice that reproducibly induces CF development when a severe colonic inflammation is obtained by intracolonic instillation of DNBS. RESULTS: Macro-microscopic observations revealed a fatty appearance of CF. Yet when compared to MAT from the same animals, CF contains very little triglycerides, few adipocytes, and we observed a very low expression and protein levels of both adipose markers (hormone-sensitive lipase, perilipin) and adipocytokines (leptin, adiponectin). The decreased expression of perilipin in CF was also observed by immunohistochemistry. Conversely, the expression of proinflammatory and fibrous markers (Pref-1) was much higher in CF than in MAT. These observations were fully consistent with those made on CF recovered from five CD patients and compared with subcutaneous and mesenteric fat from the same patients. CONCLUSIONS: Altogether, this work reports an original experimental mice model of CF. In this model we establish for the first time that CF only occurs in severe colonic inflammation and shows an inflammatory, fibrous but not an adipose pattern.


Assuntos
Tecido Adiposo/patologia , Colite/patologia , Doença de Crohn/patologia , Mesentério , Tecido Adiposo/metabolismo , Animais , Western Blotting , Peso Corporal , Colite/induzido quimicamente , Colite/metabolismo , Doença de Crohn/metabolismo , Dinitrofluorbenzeno/análogos & derivados , Dinitrofluorbenzeno/toxicidade , Ensaio de Imunoadsorção Enzimática , Humanos , Técnicas Imunoenzimáticas , Lipídeos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Peroxidase/metabolismo , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa
15.
Exp Clin Transplant ; 7(3): 164-7, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19715526

RESUMO

OBJECTIVES: Encapsulating peritoneal sclerosis is a rare but serious complication in patients undergoing peritoneal dialysis. Its mortality rate is approximately 30%, despite treatment with total parenteral nutrition, surgery, tamoxifen, or immunosuppressants. MATERIALS AND METHODS: Of 991 kidney transplants performed at our institution over 9 years, 50 patients were treated for chronic peritoneal dialysis at the time of transplant. RESULTS: Two cases of encapsulating, peritoneal sclerosis occurred in patients receiving pretransplant peritoneal dialysis. Both had received intensive posttransplant treatment for acute humoral rejection. Encapsulating peritoneal sclerosis occurred at 3 months and 4 months after the transplant. Both presented with intestinal pain and gut obstruction. They were given total parenteral nutrition plus tamoxifen (20 mg/d) for 3 months. Outcomes were favorable for 1, though there was no improvement for the second patient, who was then also given sirolimus. He died later from multiorgan failure secondary to digestive-related sepsis, and encapsulating, peritoneal, sclerosis-related symptoms. CONCLUSIONS: When encapsulating, peritoneal sclerosis occurs after kidney transplant, tamoxifen therapy could be implemented.


Assuntos
Rejeição de Enxerto/terapia , Imunidade Humoral/efeitos dos fármacos , Imunossupressores/uso terapêutico , Transplante de Rim/efeitos adversos , Diálise Peritoneal Ambulatorial Contínua/efeitos adversos , Fibrose Peritoneal/tratamento farmacológico , Plasmaferese , Tamoxifeno/uso terapêutico , Doença Aguda , Adulto , Terapia Combinada , Quimioterapia Combinada , Evolução Fatal , Rejeição de Enxerto/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/etiologia , Nutrição Parenteral Total , Fibrose Peritoneal/etiologia , Índice de Gravidade de Doença , Resultado do Tratamento
16.
Transpl Int ; 18(11): 1236-9, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16221153

RESUMO

Impact of intraoperative blood salvage autotransfusion (IBSA) on neoplastic recurrence. during liver transplantations for hepatocellular carcinoma (LT-HCC). Between January 1989 and February 2003, 16 patients received a LT-HCC without IBSA. This group was compared with 31 patients who received the same surgical procedure during the same period, but with IBSA. Data were prospectively collected. All patients had at least a 1-year postoperative follow up. Pairing was made according to the size of the largest nodule. The percentage of recurrence observed in the two groups was similar: 6.4% in the IBSA group vs. 6.3% in the group without IBSA. The median amount of transfused salvage blood was 1558 ml. The differences observed between the two groups concerned the Child score which was A in 58% patients of the IBSA group vs. 80% in the other group; the percentage of severe portal hypertension was 55% in the IBSA group vs. 31%; the median number of packed red blood cell units transfused intraoperatively was 7 in the IBSA group vs. 0, and the median number of frozen fresh plasma units transfused intraoperatively was 11 in the IBSA group vs. 4.5. It appears that IBSA, essentially used during the most haemorrhagic transplantations, could be used in the case of HCC because it does not modify the risk of neoplastic recurrence.


Assuntos
Perda Sanguínea Cirúrgica , Transfusão de Sangue Autóloga , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado , Recidiva Local de Neoplasia/epidemiologia , Adulto , Transfusão de Sangue Autóloga/efeitos adversos , Transfusão de Sangue Autóloga/estatística & dados numéricos , Carcinoma Hepatocelular/epidemiologia , Feminino , Seguimentos , Humanos , Cuidados Intraoperatórios , Cirrose Hepática/epidemiologia , Cirrose Hepática/cirurgia , Neoplasias Hepáticas/epidemiologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco
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